Acyl chloride

In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group −C(=O)Cl. Their formula is usually written R−COCl, where R is a side chain. They are reactive derivatives of carboxylic acids (R−C(=O)OH). A specific example of an acyl chloride is acetyl chloride, CH₃COCl. Acyl chlorides are the most important subset of acyl halides.

Nomenclature

Where the acyl chloride moiety takes priority, acyl chlorides are named by taking the name of the parent carboxylic acid, and substituting -yl chloride for -ic acid. Thus:

acetic acid (CH₃COOH) → acetyl chloride (CH₃COCl)

benzoic acid (C₆H₅COOH) → benzoyl chloride (C₆H₅COCl)

butyric acid (C₃H₇COOH) → butyryl chloride (C3H7COCl)

(Idiosyncratically, for some trivial names, -oyl chloride substitutes -ic acid. For example, pivalic acid becomes pivaloyl chloride and acrylic acid becomes acryloyl chloride. The names pivalyl chloride and acrylyl chloride are less commonly used, although they are arguably more logical.)

When other functional groups take priority, acyl chlorides are considered prefixes — chlorocarbonyl-:^[1]

acetic acid (CH₃COOH) → (chlorocarbonyl)acetic acid (ClOCCH₂COOH)

Properties

Lacking the ability to form hydrogen bonds, acyl chlorides have lower boiling and melting points than similar carboxylic acids. For example, acetic acid boils at 118 °C, whereas acetyl chloride boils at 51 °C. Like most carbonyl compounds, infrared spectroscopy reveals a band near 1750 cm⁻¹.

The simplest stable acyl chloride is acetyl chloride; formyl chloride is not stable at room temperature, although it can be prepared at –60 °C or below.^[2]^[3]

Acyl chlorides hydrolyze (react with water) to form the corresponding carboxylic acid and hydrochloric acid:

{\ce {RCOCl + H2O -> RCOOH + HCl}}

Synthesis

Industrial routes

The industrial route to acetyl chloride involves the reaction of acetic anhydride with hydrogen chloride:^[5]

{\ce {(CH3CO)2O + HCl -> CH3COCl + CH3CO2H}}

Propionyl chloride is produced by chlorination of propionic acid with phosgene:^[6]

{\ce {CH3CH2CO2H + COCl2 -> CH3CH2COCl + HCl + CO2}}

Benzoyl chloride is produced by the partial hydrolysis of benzotrichloride:^[7]

{\ce {C6H5CCl3 + H2O -> C6H5C(O)Cl + 2 HCl}}

Similarly, benzotrichlorides react with carboxylic acids to the acid chloride. This conversion is practiced for the reaction of 1,4-bis(trichloromethyl)benzene to give terephthaloyl chloride:

{\ce {C6H4(CCl3)2 + C6H4(CO2H)2 -> 2 C6H4(COCl)2 + 2 HCl}}

Laboratory methods: thionyl chloride

In the laboratory, acyl chlorides are generally prepared by treating carboxylic acids with thionyl chloride (SOCl₂).^[8] The reaction is catalyzed by dimethylformamide and other additives.^[9]^[10]

Thionyl chloride^[11]⁠ is a well-suited reagent as the by-products (HCl, SO₂) are gases and residual thionyl chloride can be easily removed as a result of its low boiling point (76 °C).

Laboratory methods: phosphorus chlorides

Phosphorus trichloride (PCl₃) is popular,^[12] although excess reagent is required.^[9] Phosphorus pentachloride (PCl₅) is also effective,^[13]^[14] but only one chloride is transferred:

{\ce {RCO2H + PCl5 -> RCOCl + POCl3 + HCl}}

Laboratory methods: oxalyl chloride

Another method involves the use of oxalyl chloride:

{\ce {RCO2H + ClCOCOCl -> RCOCl + CO + CO2 + HCl}}

The reaction is catalysed by dimethylformamide (DMF), which reacts with oxalyl chloride to give the Vilsmeier reagent, an iminium intermediate that which reacts with the carboxylic acid to form a mixed imino-anhydride. This structure undergoes an acyl substitution with the liberated chloride, forming the acid anhydride and releasing regenerated molecule of DMF.^[10] Relative to thionyl chloride, oxalyl chloride is more expensive but also a milder reagent and therefore more selective.